Colchicine for stroke prevention in patients with coronary artery disease: a systematic review and meta-analysis.

BACKGROUND AND PURPOSE: Although clinical trials suggest that colchicine may reduce the risk of vascular events in patients with a history of coronary artery disease, its effect on the prevention of cerebrovascular events still remains unclear. METHODS: A systematic review and meta-analysis was performed of all available randomized controlled trials (RCTs) reporting on incident strokes during the follow-up of patients with a history of cardiovascular disease randomized to colchicine treatment or control (placebo or usual care). RESULTS: Four RCTs were identified, including a total of 5553 patients (mean age 61 years, 81% males), with a follow-up ranging from 1 to 36 months. Colchicine treatment was associated with a significantly lower risk of incident stroke during follow-up compared to control (risk ratio 0.31, 95% confidence interval 0.13-0.71), without heterogeneity across included studies (I2  = 0%). Based on the pooled incident stroke rate of control groups (0.9%) in the included RCTs, it was estimated that administration of low-dose colchicine to 161 patients with coronary artery disease would prevent one stroke during a follow-up of 23 months. CONCLUSION: Colchicine treatment decreases stroke risk in patients with a history of coronary artery disease. The effect of colchicine in secondary stroke prevention is currently being evaluated in an ongoing RCT.

Meta-analysis of risk factors and complications associated with atrial fibrillation after oesophagectomy.

BACKGROUND: Oesophagectomy is associated with high morbidity and mortality rates. New-onset atrial fibrillation (AF) is a frequent complication following oesophagectomy. Several studies have explored whether new-onset AF is associated with adverse events after oesophagectomy. METHODS: This review was performed according to PRISMA guidelines. Eligible studies were identified through a search of PubMed, Scopus and Cochrane CENTRAL databases up to 25 November 2018. A meta-analysis was conducted with the use of random-effects modelling. The I2 statistic was used to assess for heterogeneity. RESULTS: In total, 53 studies including 9087 patients were eligible for analysis. The overall incidence of postoperative AF was 16·5 per cent. Coronary artery disease and hypertension were associated with AF, whereas diabetes, smoking and chronic obstructive pulmonary disease were not. Patients with AF had a significantly higher risk of overall postoperative adverse events than those without fibrillation (odds ratio (OR) 5·50, 95 per cent c.i. 3·51 to 8·30), including 30-day mortality (OR 2·49, 1·70 to 3·64), anastomotic leak (OR 2·65, 1·53 to 4·59) and pneumonia (OR 3·42, 2·39 to 4·90). CONCLUSION: Postoperative AF is frequently observed in patients undergoing oesophagectomy for cancer. It is associated with an increased risk of death and postoperative complications.

Restless legs syndrome and cerebrovascular/cardiovascular events: Systematic review and meta-analysis.

OBJECTIVE: We performed a systematic review and meta-analysis to evaluate the proposed association of restless legs syndrome (RLS) with cerebrovascular/cardiovascular outcomes. METHODS: We calculated the corresponding odds ratios on the prevalence of cerebrovascular/cardiovascular risk factors and standardized mean differences on the reported mean age at baseline between RLS patients and controls. We also calculated the corresponding risk ratios and adjusted for potential confounders hazard ratios (HRsadjusted ) on the reported outcomes of interest between RLS patients and controls. RESULTS: We identified 8 eligible studies (644 506 patients, mean age: 60.2 years, 36.2% males; 3.3% with RLS). RLS patients were found to have significantly higher prevalence of hypertension (P = .002), diabetes (P = .003) and hyperlipidemia (P = .010) compared to controls. In the unadjusted analyses of prospective observational studies, RLS patients were found to have significantly higher risk for cerebrovascular ischaemia (P = .01) and all-cause mortality (P = .04) compared to controls during follow-up, while in the adjusted for potential confounders analyses RLS patients were only found to have a higher risk of all-cause mortality (HR adjusted=1.52, 95% CI: 1.17-1.97, P = .002). CONCLUSIONS: The present report does not provide evidence for an increased risk of cerebrovascular and cardiovascular events in RLS patients, which highlights the vast presence of confounding factors.

Intravenous thrombolysis for patients with in-hospital stroke onset: propensity-matched analysis from the Safe Implementation of Treatments in Stroke-East registry.

BACKGROUND AND PURPOSE: Recent cross-sectional study data suggest that intravenous thrombolysis (IVT) in patients with in-hospital stroke (IHS) onset is associated with unfavorable functional outcomes at hospital discharge and in-hospital mortality compared to patients with out-of-hospital stroke (OHS) onset treated with IVT. We sought to compare outcomes between IVT-treated patients with IHS and OHS by analysing propensity-score-matched data from the Safe Implementation of Treatments in Stroke-East registry. METHODS: We compared the following outcomes for all propensity-score-matched patients: (i) symptomatic intracranial hemorrhage defined with the safe implementation of thrombolysis in stroke-monitoring study criteria, (ii) favorable functional outcome defined as a modified Rankin Scale (mRS) score of 0-1 at 3 months, (iii) functional independence defined as an mRS score of 0-2 at 3 months and (iv) 3-month mortality. RESULTS: Out of a total of 19 077 IVT-treated patients with acute ischaemic stroke, 196 patients with IHS were matched to 5124 patients with OHS, with no differences in all baseline characteristics (P > 0.1). Patients with IHS had longer door-to-needle [90 (interquartile range, IQR, 60-140) vs. 65 (IQR, 47-95) min, P < 0.001] and door-to-imaging [40 (IQR, 20-90) vs. 24 (IQR, 15-35) min, P < 0.001] times compared with patients with OHS. No differences were detected in the rates of symptomatic intracranial hemorrhage (1.6% vs. 1.9%, P = 0.756), favorable functional outcome (46.4% vs. 42.3%, P = 0.257), functional independence (60.7% vs. 60.0%, P = 0.447) and mortality (14.3% vs. 15.1%, P = 0.764). The distribution of 3-month mRS scores was similar in the two groups (P = 0.273). CONCLUSIONS: Our findings underline the safety and efficacy of IVT for IHS. They also underscore the potential of reducing in-hospital delays for timely tissue plasminogen activator delivery in patients with IHS.

The diagnostic yield of transesophageal echocardiography in patients with cryptogenic cerebral ischaemia: a meta-analysis.

BACKGROUND AND PURPOSE: The diagnostic utility of transesophageal echocardiography (TEE) in patients with cryptogenic ischaemic stroke (IS) or transient ischaemic attack (TIA) remains controversial. METHODS: A systematic review and meta-analysis was performed according to PRISMA guidelines to estimate the pooled prevalence of potential cardioembolic causes detected by TEE in prospective observational studies of cryptogenic IS/TIA. Cardiac conditions causally associated with cerebral ischaemia were considered to be intramural thrombi and intracardiac tumors according to ASCO phenotyping of IS. RESULTS: Thirty-five eligible studies, comprising 5772 patients (mean age 53.6 years, 56.9% men) were identified. The most common TEE finding was ascending aorta and/or aortic arch atheroma [51.2% (27.4%-74.5%)], followed by patent foramen ovale (PFO) [43.2% (36.3%-50.4%)]. Complex aortic plaques and large PFOs were reported in 14% (10.2%-18.9%) and 19.5% (16.6%-22.8%) of TEE evaluations. The prevalence of atrial septal aneurysm was 12.3% (7.9%-18.7%) and was significantly higher in conjunction with PFO presence (risk ratio 2.04, 95% confidence interval 1.63-2.54, P < 0.001). The prevalence of left atrial thrombus [3.0% (1.1%-8.3%)] and spontaneous echo contrast [3.8% (2.3%-6.2%)] was low. The prevalence of intracardiac tumors was extremely uncommon [0.2% (0%-0.7%)]. Significant heterogeneity was identified (I(2) > 60%) in the majority of analyses. Heterogeneity was not affected by cryptogenic stroke definition (TOAST versus alternative criteria). After dichotomizing available studies using a cut-off of 50 years, PFO was significantly (P = 0.001) more prevalent in younger than in older patients. CONCLUSION: Routine TEE in patients with cryptogenic IS/TIA commonly identifies abnormal findings. However, the prevalence of cardiac conditions considered to be causally associated with cerebral ischaemia (intracardiac thrombi and tumors) is low.

Apolipoprotein E polymorphisms and ischaemic stroke: a two-center Greek study.

BACKGROUND AND PURPOSE: Apolipropotein E(apoE) is a plasma protein exhibiting three common isoforms (E2, E3, E4). Its involvement in lipoprotein metabolism may have an impact on stroke occurrence. As results in the literature are inconclusive further studies are needed to elucidate its role. Our objective was to study the role of apoE isoforms and the interplay with environmental risk factors in patients with first ischaemic stroke occurrence in the Greek population. METHODS: Three hundred and twenty-nine patients with first-ever ischaemic stroke were included in our study. Strokes of cardioembolic origin and patients with autoimmune or prothrombotic syndromes were excluded. A control group of 361 subjects with no stroke history were also included in our study. Risk factors (hyperlipidemia, hypertension, diabetes mellitus and smoking) were assessed. ApoE alleles were determined in all subjects participating in the study. RESULTS: Genotype ε3/ε3 was found to have a protective role against stroke occurrence compared with other genotypes (odds ratio 0.674, 95% confidence interval 0.480-0.946) especially in the female patient subgroup. In multivariate analysis after adjustment for age, body mass index (BMI), hypertension, dyslipidemia, diabetes mellitus and smoking, the role of genotype was limited and outweighed by risk factors in both genders. No association between apoE alleles and BMI, cholesterol, triglycerides or high-density lipoprotein plasma levels was noted. CONCLUSIONS: Our study was indicative of a protective role of the ε3/ε3 genotype, especially in female patients. However, risk factors such as age, BMI, hypertension, dyslipidemia, diabetes mellitus and smoking have a strong impact on stroke occurrence and outweigh the protective role of the ε3/ε3 genotype.

Cerebral sinus venous thrombosis in inflammatory bowel diseases.

BACKGROUND: It has been estimated that 1.3-6.4% of patients with inflammatory bowel diseases (IBD) are complicated by cerebral venous thrombosis (CVT) at some point of time during the course of their disease. METHODS: We retrospectively reviewed and subsequently analyzed data from 65 case reports of IBD patients with CVT. Our sources included MEDLINE and EMBASE, and the references of retrieved articles were also screened. RESULTS: Patients with CVT and IBD were significantly younger than CVT patients without IBD. Female patients were complicated more frequently but at an older age when compared with males. The incidence of ulcerative colitis was almost double compared with Crohn's disease. Active disease was detected in 78.4% of the cases and the proportions of patients with active ulcerative colitis or active Crohn's disease were almost equal. The predominant neurological symptom in these patients was persistent headache (80%) and the most common site of CVT was the superior sagittal sinus (50.7%). Severe iron deficiency anemia was highlighted as a significant risk factor for thrombosis in nearly half of the patients. Transient coagulation abnormalities and hereditary thrombogenic mutations were identified in 23 and 20% of the case reports, respectively. CONCLUSION: The overall outcome was very good, especially in those patients who were treated acutely with heparin or low molecular weight heparin, suggesting that heparin administration is related with improved neurological outcome and decreased mortality rates even in IBD patients complicated with CVT.

Voxel-based diffusion tensor imaging detects pyramidal tract degeneration in primary lateral sclerosis.

OBJECTIVE: Primary lateral sclerosis (PLS) is a progressive degenerative disorder affecting upper motor neurons and requires a clinical diagnosis. Diffusion tensor imaging (DTI) is a quantitative method for assessing white matter fibre integrity. The purpose of the study was to evaluate the involvement of upper motor neurons by using DTI in PLS. METHODS: A patient with PLS was compared with eight age-matched controls. Differences in fractional anisotropy (FA) index were assessed using DTI on a voxel-by-voxel basis. RESULTS: Decreased FA was observed in the proximal part of the pyramidal tract bilaterally, which indicated degeneration of the pyramidal cells. CONCLUSION: Voxel-based DTI could be used as an objective marker for detecting upper motor neuron degeneration in PLS.

Metabolic syndrome and cerebral vasomotor reactivity.

BACKGROUND AND PURPOSE: Metabolic syndrome has been proposed as a risk factor for stroke and transient ischaemic attack. One pathophysiological mechanism could be impairment of endothelial function. Thus, we hypothesized that cerebral vasomotor reactivity would be decreased in patients with metabolic syndrome, compared to patients without metabolic syndrome. METHODS: In this retrospective analysis, 83 consecutive patients (aged 59.19 ± 15.98; 33 women) underwent Doppler examination for carotid artery disease including bi-hemispherical vasomotor reactivity assessment using transcranial Doppler monitoring. Vasomotor reactivity data were analyzed from the hemisphere with no or low-grade carotid stenosis (<40%). Cerebral vasomotor reactivity was calculated as percent increase in mean flow velocity per mmHg pCO(2) during 2 min of 5% CO(2) inhalation delivered by anesthesia mask (normal if ≥ 2%/mmHg). Univariate and multivariable linear regression models were used to determine factors, including metabolic syndrome, that were independently associated with pathologic vasomotor reactivity. RESULTS: After adjusting for the presence of contralateral carotid stenosis and ipsilateral stroke in the multivariable model, metabolic syndrome was independently associated with lower vasomotor reactivity values (2.27 ± 1.24% vs. 2.68 ± 1.37; ß = -0.258, P = 0.033). In this model, there was no association of cerebral vasomotor reactivity with age, gender, race, cardiac disease, current statin therapy, or small vessel disease. CONCLUSIONS: Our findings suggest that impaired cerebral vasomotor reactivity may be a mediator of stroke in patients with metabolic syndrome, a syndrome affecting a significant and growing proportion of the population. A prospective longitudinal study is warranted to study the cerebral haemodynamic effect of metabolic syndrome.

Statin therapy after first stroke reduces 10-year stroke recurrence and improves survival.

OBJECTIVE: To determine whether statin therapy after hospital discharge affects ischemic stroke recurrence and long-term mortality in patients admitted for a first-ever occurrence of ischemic stroke. METHODS: This was a retrospective observational study involving linked hospitalization and death records. The cohort comprised a series of 794 consecutive, first-ever acute ischemic stroke patients from the Athenian Stroke Registry, admitted to the acute stroke unit and the general medicine and neurology ward of our institutions since January 1997 for whom there was available information covering a 10-year follow-up period. Cox proportional hazards model was used to identify risk factors for stroke recurrence and death. RESULTS: The recurrence rate was 16.3% among stroke patients not receiving a statin after hospital discharge compared with 7.5% among those who received statin therapy (p = 0.002). Cox regression analyses revealed only statin therapy postdischarge to be a significant independent predictor of stroke recurrence (adjusted hazard ratio [HR], 0.65, 95% confidence interval [CI] 0.39 to 0.97, p < 0.01). Similarly, patients receiving a statin had a significantly lower mortality during the 10-year period after the acute cerebrovascular event (adjusted HR, 0.43; 95% CI 0.29 to 0.61, p < 0.01). CONCLUSIONS: Prescribing statin therapy upon hospital discharge to patients with first-ever acute stroke lowers the risk of 10-year stroke recurrence and improves survival.

The use of radioisotopes for palliation of metastatic bone pain.

Bone pain associated with advanced prostate and other cancers is a frequent and significant complication. Pharmaceutical therapy of bone pain includes nonsteroidal analgesics and opiates. While external beam radiation therapy remains the mainstay of pain palliation of solitary lesions, bone-seeking radiopharmaceuticals have entered the armamentarium for the treatment of multiple osseous metastases. The 3 radioisotopes currently approved for treatment of pain (strontium-89/(89)Sr, samarium-153/(153)Sm and rhenium-186/(186)Re) are discussed in this review including the approved dose, method of administration and indications for use.

Association of estrogen receptor-alpha gene polymorphisms with stroke risk in patients with metabolic syndrome.

OBJECTIVE: The vascular protective effects of estrogens are mediated by their binding to the two known estrogen receptors. In this study, we examine the association of stroke with two common polymorphisms of the ESR1 gene in patients with metabolic syndrome. MATERIALS AND METHODS: DNA from 130 patients hospitalized for ischemic stroke and 240 healthy controls were genotyped for ESR1 PvuII and XbaI polymorphisms. Results - Comparing female and male patients, it was found that CCGG diplotype is more frequent in male patients (P = 0.03). In addition, the AA genotype is associated with the onset of stroke at a younger age in the male patient group (P < 0.05). CONCLUSIONS: These findings suggest that PvuII and XbaI polymorphisms may affect the age at onset of the first stroke and the probability of developing cerebrovascular disease.

Guillain-Barré syndrome in northwest Greece.

OBJECTIVES: We present the epidemiological and clinical-laboratory features of Guillain-Barré syndrome (GBS) in northwest Greece over a 9.5-year period. MATERIALS AND METHODS: We studied all the patients with GBS who were admitted to our neurology inpatient service from January 1996 to May 2005 and compared them with previously published series. RESULTS: Forty-six patients were hospitalized during this period. The average crude incidence rate was 1.22/100,000 populations per year, and males were more susceptible than females. There was a spring clustering, as 52.17% presented the syndrome during spring. The axonal type of GBS was recorded in 13.04% of the patients. The most frequent presenting symptom was dysesthetic numbness (52.17%). A large number of patients (56.52%) had up to three times the elevation of liver function values that resolved in a few weeks. Most patients had an excellent recovery and no deaths were recorded. CONCLUSIONS: In our series, there was no difference in the incidence rate and subtypes of GBS but there was a significant seasonality with spring clustering. A transient elevation of transaminases of undetermined etiology was noted in more than a half of our patients. Although seven patients (15.21%) had significant neurologic sequelae, no deaths occurred.

A method for classification of transient events in EEG recordings: application to epilepsy diagnosis.

OBJECTIVES: The aim of the paper is to analyze transient events in inter-ictal EEG recordings, and classify epileptic activity into focal or generalized epilepsy using an automated method. METHODS: A two-stage approach is proposed. In the first stage the observed transient events of a single channel are classified into four categories: epileptic spike (ES), muscle activity (EMG), eye blinking activity (EOG), and sharp alpha activity (SAA). The process is based on an artificial neural network. Different artificial neural network architectures have been tried and the network having the lowest error has been selected using the hold out approach. In the second stage a knowledge-based system is used to produce diagnosis for focal or generalized epileptic activity. RESULTS: The classification of transient events reported high overall accuracy (84.48%), while the knowledge-based system for epilepsy diagnosis correctly classified nine out of ten cases. CONCLUSIONS: The proposed method is advantageous since it effectively detects and classifies the undesirable activity into appropriate categories and produces a final outcome related to the existence of epilepsy.

Bilateral thalamic infarcts presenting as acute pseudobulbar palsy.

A 28-year-old, previously healthy, normotensive woman suddenly developed an acute pseudobulbar palsy with dysarthria, dysphagia, hypernasal voice and mild right arm paresis. Extensive laboratory investigations excluded all other possible causes of acute pseudobulbar palsy (neoplastic, inflammatory, demyelinative, myasthenic) and an MRI study demonstrated bilateral isolated thalamic infarcts. Oral contraceptives and smoking were the only possible stroke risk factors found and cerebral diaschisis the most tenuous explanation proposed. To our knowledge, this is the first report indicating that bilateral thalamic infarction on specific nuclei could be manifested as acute pseudobulbar palsy.

Delayed diagnosis of spinal vascular malformations presenting as intermittent myelopathy.

We report our recent experience of three male patients, whose clinical diagnosis and subsequent surgery was delayed for 9.25 and 15 months respectively. Initially, they all presented with vague, either sensory or motor lower limb disturbances and intermittency of symptoms was followed by bladder dysfunction or impotence. Extensive laboratory work-up was unrevealing and the non-specific diagnosis of myelopathy further delayed the recognition of the underlying vascular lesion. Finally spinal magnetic resonance imaging (MRI), supine myelography and selective spinal arteriography indicated the presence of a tumor in the first patient and vascular malformation in the other two. Neurosurgery and histology confirmed one cavernous angioma and two arteriovenous malformations, all thoracic and dural. We believe that both the cryptic nature of these lesions and our technical limitations (spinal arteriography and MRI not readily available), accounted for the delayed diagnosis in our three patients, who nevertheless, when treated by surgery showed a satisfactory outcome in the first case, while further deterioration was prevented in the other two.